Preclinical Evaluation of a Novel Series of Polyfluorinated Thalidomide Analogs in Drug-Resistant Multiple Myeloma.

Immunomodulatory imide drugs (IMiDs) play a crucial role in the treatment landscape across various stages of multiple myeloma. Despite their evident efficacy, some patients may exhibit primary resistance to IMiD therapy, and acquired resistance commonly arises over time leading to inevitable relapse. It is critical to develop novel therapeutic options to add to the treatment arsenal to overcome IMiD resistance. We designed, synthesized, and screened a new class of polyfluorinated thalidomide analogs and investigated their anti-cancer, anti-angiogenic, and anti-inflammatory activity using in vitro and ex vivo biological assays. We identified four lead compounds that exhibit potent anti-myeloma, anti-angiogenic, anti-inflammatory properties using three-dimensional tumor spheroid models, in vitro tube formation, and ex vivo human saphenous vein angiogenesis assays, as well as the THP-1 inflammatory assay. Western blot analyses investigating the expression of proteins downstream of cereblon (CRBN) reveal that Gu1215, our primary lead candidate, exerts its activity through a CRBN-independent mechanism. Our findings demonstrate that the lead compound Gu1215 is a promising candidate for further preclinical development to overcome intrinsic and acquired IMiD resistance in multiple myeloma.

Unexpected TEE Findings During Rheumatic Triple-Valve Surgery: Incidental, Yet Impactful.

This E-Challenge highlights an incidental prebypass transesophageal echocardiographic (TEE) finding of a right atrial membrane that impacted cardiac surgical management during triple-valve surgery. Two-dimensional and advanced 3-dimensional (3D) TEE were used in real-time to assist intraoperative decision-making. The findings, clinical course, discussion of the differential diagnosis, final diagnosis, and patient management are detailed here.

Barriers to atrial fibrillation ablation during mitral valve surgery.

BACKGROUND: Nearly 40% of patients with atrial fibrillation (AF) undergoing mitral valve surgery do not receive concomitant ablation despite societal guidelines. We assessed barriers to implementation of this evidence-based practice through a survey of cardiac surgeons in 2 statewide quality collaboratives. METHODS: Adult cardiac surgeons across 2 statewide collaboratives were surveyed on their knowledge and practice regarding AF ablation. Questions concerning experience, clinical practice, case scenarios, and barriers to implementation were included. RESULTS: Among 66 respondents (66 of 135; 48.9%), the majority reported "very comfortable/frequently use" cryoablation (53 of 66; 80.3%) and radiofrequency (55 of 66; 83.3%). Only 12.1% (8/66) were not aware of the recommendations. Approximately one-half of the respondents reported learning AF ablation in fellowship (50.0%; 33 of 66) or attending courses (47.0%; 31 of 66). Responses to clinical scenarios demonstrated wide variability in practice patterns. One-half of the respondents reported no barriers; others cited increased cross-clamp time, excessive patient risk, and arrhythmia incidence as obstacles. Desired interventions included cardiology/electrophysiology support, protocols, pacemaker rate information, and education in the form of site visits, videos and proctors. CONCLUSIONS: Knowledge of evidence-based recommendations and practice patterns vary widely. These data identify several barriers to implementation of concomitant AF ablation and suggest specific interventions (mentorship/support, protocols, research, and education) to overcome these barriers.

Undersizing mitral annuloplasty alters left ventricular mechanics in a swine model of ischemic mitral regurgitation.

OBJECTIVE: Undersizing mitral annuloplasty (UMA) is a frequently used surgical repair technique to correct ischemic mitral regurgitation in patients with heart failure. In this study, we sought to test the hypothesis that downsizing the mitral annulus can adversely affect the shape and mechanics of the left ventricle inhibiting its functional recovery. METHODS: Eighteen farm swine that underwent an inferolateral myocardial infarction and developed ischemic mitral regurgitation of >2+ severity after 2 months were assigned as follows: 9 swine received an undersized mitral annuloplasty, 6 received papillary muscle approximation (PMA), and 3 animals did not receive any other intervention. Animals lived another 3 months and cardiac magnetic resonance imaging was performed before termination to assess ventricle mechanics and function. RESULTS: Ejection fraction was comparable between the 2 repair groups before surgery, but was significantly lower in UMA at 38.89% ± 7.91% versus 50.83% ± 9.04% in the PMA group (P = .0397). Animals receiving UMA had lower regional peak fractional shortening and reduced systolic and diastolic radial velocities compared with PMA and in some regions were lower than sham. Animals that underwent UMA had higher circumferential strain than sham, but lower than PMA. UMA animals have lower longitudinal strain compared to sham group and lower LV torsion than PMA. CONCLUSIONS: Undersizing the mitral annulus with an annuloplasty ring can restore valvular competence, but unphysiologically impair ventricle mechanics. Mitral valve repair strategies should focus not only on restoring valve competence, but preserving ventricle mechanics.

Fulminant cardiogenic shock due to cardiac sarcoidosis.

This case describes a 57-year-old man with unrecognized cardiac sarcoidosis who presented with progressive heart failure leading to cardiogenic shock. He required extracorporeal membrane oxygenation (ECMO) as a bridge to orthotopic heart transplantation. The case highlights the potential acute and severe electrical and hemodynamic manifestations of cardiac sarcoidosis.

Papillary Muscle Approximation Reduces Systolic Tethering Forces and Improves Mitral Valve Closure in the Repair of Functional Mitral Regurgitation.

Background: Undersizing mitral annuloplasty (UMA) to repair functional mitral regurgitation lacks durability, as it forces leaflet coaptation without relieving the sub-leaflet tethering forces. In this biomechanical study, we demonstrate that papillary muscle approximation (PMA) prior to UMA can drastically relieve tethering forces and improve valve function, without the need for significant annular downsizing. Methods: An ex vivo model of functional mitral regurgitation (FMR) was used, in which pig mitral valves were geometrically perturbed to induce FMR, and the repairs were performed. Nine pig mitral valves were studied as follows: normal(baseline), functional mitral regurgitation (FMR), true-sized annuloplasty to 30mm (TSR), and undersized annuloplasty to 26mm (DSR); and concomitant papillary muscle approximation (PMA) at both ring sizes. Mitral regurgitation, valve kinematics, and chordal forces were measured and compared between groups. Results: FMR geometry induced a 16.31±7.33% regurgitant fraction, compared to none at baseline. 30mm/TSR reduced regurgitation to 6.05±5.63% and a 26mm/DSR to 5.06±6.76%. Addition of papillary muscle approximation prior to either rings, reduced regurgitation to 3.87±6.79% with the true sized ring (TSR+PMA), and 3.71±6.25% with the downsized ring (DSR+PMA). Peak anterior and posterior marginal chordal forces were elevated to 0.09±0.1N and 0.12±0.1N respectively with FMR, which were not reduced by annuloplasty of either sizes. Addition of PMA, reduced the forces significantly to 0.23±0.02N and 0.51±0.04N. Conclusion: This biomechanical study, demonstrates that papillary muscle approximation relieves tethering forces and when added to annuloplasty, and mobilizes the leaflets to achieve a good valve closure. Such a result could be achieved without the need for extensive annular downsizing.

Sarcopenia and health-related quality of life in older adults after transcatheter aortic valve replacement.

BACKGROUND: Skeletal muscle wasting, or sarcopenia, affects a significant proportion of patients undergoing transcatheter aortic valve replacement (TAVR). However, its influence on post-TAVR recovery and 1-year health-related quality of life (HR-QOL) remains unknown. We examined the relationship between skeletal muscle index (SMI), post-TAVR length of hospital stay (LOS), and 1-year QOL. METHODS: The study sample consisted of 300 consecutive patients undergoing TAVR from 2012 to 2018 who had pre-TAVR computed tomographic scans suitable for analysis of body composition. Skeletal muscle mass was quantified as cm2 of skeletal mass per m2 of body surface area from the cross-sectional computed tomographic image at the third lumbar vertebra. Sarcopenia was defined using established sex-specific cutoffs (women: SMI < 39 cm2/m2; men: < 55 cm2/m2). Multivariable linear regression analysis was used to determine the relationship between SMI, LOS, and HR-QOL using the Kansas City Cardiomyopathy Questionnaire. RESULTS: Sarcopenia was present in most (59%) patients and associated with older age (82 vs 76 years; P < .001) and lower body mass index (27 vs 33 kg/m2; P < .001). There were no other differences in baseline clinical or echocardiographic characteristics among the 4 quartiles of SMI. SMI was positively correlated with LOS and 1-year QOL. After adjusting for age, gender, race, and body mass index, SMI remained a significant predictor of both LOS (P = .01) and 1-year QOL (P = .012). For every 10 cm2/m2 higher SMI, there was an 8-point increase in Kansas City Cardiomyopathy Questionnaire score, a difference that is clinically meaningful. CONCLUSIONS: Sarcopenia is prevalent in TAVR patients. Higher SMI is associated with shorter LOS and better 1-year HR-QOL. To achieve optimal TAVR benefits, further study into how body composition influences post-TAVR recovery and durable improvement in QOL is warranted.

Incidence, Prognosis and Predictors of Major Vascular Complications and Percutaneous Closure Device Failure Following Contemporary Percutaneous Transfemoral Transcatheter Aortic Valve Replacement.

OBJECTIVES: To determine the incidence, prognosis, and predictors of major Valve Academic Research Consortium (VARC-2) vascular complications (VCs) and percutaneous vascular closure device failure (PCDF) following contemporary percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: Limited data exists on the incidence and predictors of VCs and PCDFs following percutaneous TF-TAVR using contemporary 14-16 French (F) sheaths. METHODS: We recorded clinical and procedural characteristics, computer tomography (CT) angiographic data, 30-day VCs, mortality, and length of stay (LOS) in all consecutive percutaneous TF-TAVRs at a single center from June 2016 to October 2018. CT measures included common femoral artery (CFA) and external iliac artery (EIA) diameters, sheath to CFA and EIA ratios (SFAR and SEIAR), depth of CFA, extent and location of CFA calcification and pelvic vessel tortuosity (2 bends ≥90°). Multivariable regression was used to predict major VCs and percutaneous closure device failure (PCDF), respectively. RESULTS: The final sample consisted of 303 percutaneous TF-TAVRs. Median age was 80 years, 51% were male, 86% Caucasian, 33% had diabetes mellitus (DM) and mean STS score was 5.8 ±â€¯3.8%. Baseline characteristics were similar in patients with vs. without VCs, other than coronary artery disease (CAD) (69% vs. 54%, respectively; p = 0.029) and DM (21% vs. 36%, respectively; p = 0.02). There were 65 (21%) vascular complications: 19 major VCs [6.3%], 29 minor [VCs 9.6%] and 17 PCDFs [5.6%]. Overall, 30-day mortality was low (2.6%). Major VCs were associated with higher mortality (42% vs. 0%, p < 0.0001) while minor VCs (3% vs. 0%, mortality p = 0.99) and PCDFs (3% vs. 0% mortality, p = 0.99) were not. PCDFs were associated with a longer median LOS (4 vs. 3 days, p = 0.02). The independent predictors of major VCs were pelvic vessel tortuosity (OR 3.1; 95% CI 1.1-9.2) and presence of CAD (OR 8.2; 95% CI 1.8-37). Female gender showed a strong trend toward increased risk (OR 3.4; CI 0.84-14; p = 0.086). There were no independent predictors of PCDF. CONCLUSION: Contemporary percutaneous TF-TAVR is associated with a low risk of mortality, major VCs and PCDFs. Major VCs confer increased mortality and PCDFs prolong LOS. Pelvic vessel tortuosity and a history of CAD predict major VCs; there were no predictors of PCDFs. These results provide a contemporary update on the incidence and implications of these important vascular complications in the current era of percutaneous TF-TAVR using 14-16F vascular sheaths.

Examination of a Proposed 30-day Readmission Risk Score on Discharge Location and Cost.

BACKGROUND: Readmissions cost an estimated $41 billion in the United States each year. To address this, a single institution recently developed a new risk model predictive of 30-day readmission after adult cardiac surgery. The purpose of this study is to validate and refine this new readmission risk model using a statewide database. METHODS: A total of 19,964 patients were analyzed using a statewide Society of Thoracic Surgeons database (2014-2017). The aforementioned multivariate model was replicated (model 1): race, hospital length of stay, chronic lung disease, operation type, and renal failure. Model 2 also included discharge location. Thirty-day readmission risk scores and low-risk (0%-10%), moderate-risk (10%-13%), and high-risk (≥13%) categories were calculated. RESULTS: The overall 30-day readmission rate was 11.1% with both models 1 and 2 predicting readmission (odds ratio, 1.09; 95% confidence interval, 1.08-1.11 vs odds ratio, 1.10; 95% confidence interval, 1.08-1.11). Statistically significant differences were observed across all risk categories in discharge location and total cost. For models 1 and 2, 86% of low-risk patients were discharged to home vs 66.9% and 42.9% of patients in high-risk groups, respectively (P < .001). The largest increases were observed with a hospice discharge location for both model 1 (from $37,930 to $89,285) and model 2 (from $37,930 to $89,230). CONCLUSIONS: Both risk models significantly predicted 30-day readmission in our multiinstitutional dataset, confirming the score is valid and a generalizable quality improvement tool. The addition of discharge location and total cost adds valuable information of the ongoing efforts to identify patients at high risk for readmission.

Mid-Term Outcomes of Transcatheter Aortic Valve Replacement in Extremely Large Annuli With Edwards SAPIEN 3 Valve.

OBJECTIVES: The aim of this study was to report the 1-year results of transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 (S3) valve in extremely large annuli. BACKGROUND: Favorable 30-day outcomes of S3 TAVR in annuli >683 mm2 have previously been reported. Pacemaker implantation rates were acceptable, and a larger left ventricular outflow tract and more eccentric annular anatomy were associated with increasing paravalvular leak. METHODS: From December 2013 to December 2018, 105 patients across 15 centers with mean area 721.3 ± 36.1 mm2 (range 683.5 to 852.0 mm2) underwent TAVR using an S3 device. Clinical, anatomic, and procedural characteristics were analyzed. One-year survival and echocardiographic follow-up were reached in 94.3% and 82.1% of patients, respectively. Valve Academic Research Consortium-2 30-day and 1-year outcomes were reported. RESULTS: The mean age was 76.9 ± 10.4 years, and Society of Thoracic Surgeons predicted risk score averaged 5.2 ± 3.4%. One-year overall mortality and stroke rates were 18.2% and 2.4%, respectively. Quality-of-life index improved from baseline to 30 days and at 1 year (p < 0.001 for both). Mild paravalvular aortic regurgitation occurred in 21.7% of patients, while moderate or greater paravalvular aortic regurgitation occurred in 4.3%. Mild and moderate or severe transvalvular aortic regurgitation occurred in 11.6% and 0%, respectively. Valve gradients remained stable at 1 year. CONCLUSIONS: S3 TAVR in annular areas >683 mm2 is feasible, with favorable mid-term outcomes.

Frailty in the Cardiac Surgical Patient: Comparison of Frailty Tools and Associated Outcomes.

BACKGROUND: Frailty measurement in cardiac surgery is poorly studied. The study purposes were to identify a simple but accurate frailty tool by comparing the simplified frailty index, Study of Osteoporotic Fractures (SOF), to a more complex frailty index, the Cardiovascular Health Study (CHS), and outcomes of frail patients to nonfrail patients. METHODS: Patients aged 65 years or older admitted for elective coronary artery bypass grafting (CABG), valvular surgery (valve), or a combination of CABG/valve were recruited and administered the SOF and CHS indexes. Surgical outcomes were defined by The Society of Thoracic Surgeons. A hand-held dynamometer assessed grip strength. Health-related quality of life was assessed by the 12-Item Short Form Health Survey. RESULTS: Patients (n = 167) were primarily male (75%), white (88%), and CABG (23%), valve (50%), or CABG/valve (25%). Frailty agreement between the CHS (frail, n = 47) and SOF (frail, n = 15) was poor (κ = 0.185). SOF frail patients had poorer health, were men (67% vs 61%), had a decreased ejection fraction (0.467 vs 0.537), an increased Society of Thoracic Surgeons Risk (5.0 vs 3.5), and increased European System for Cardiac Operative Risk Evaluation score (8.2 vs 5.2). All SOF frail patients reported lack of energy vs 8.7% CHS frail patients, and 80% vs 23.9% reported an unintentional weight loss of 5% or more. SOF frail patients were significantly more likely to experience prolonged ventilation (20% vs 6.5%), pneumonia (20% vs 6.5%), prolonged intensive care unit hours (158.6 vs 85.01), and readmission within 30 days (20% vs 8.7%). All frail patients reported a significantly lower physical health-related quality of life. CONCLUSIONS: The SOF tool better identified patients considered "frail." Frail patients had more adverse outcomes and poorer health-related quality of life.

Confirmatory factor analysis of the Minnesota living with heart failure questionnaire among patients following open heart surgery for valve dysfunction.

INTRODUCTION: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was designed to assess the impact of the adverse effects of heart failure (HF). Numerous reports suggest an additional third factor with the proposed third factor representing a social dimension. The purpose of this study was to use confirmatory factor analysis (CFA) to validate the factor structure of the MLWHFQ, and examine a proposed third factor structure. METHODS: Participants were 1290 individuals with open heart surgery for isolated valve repair or replacement between September 2005 and May 2016. Confirmatory factor analysis was used to assess both initial and proposed alternate factor structures. RESULTS: CFA indicated a poor fit for the original proposed 2-factor solution [root mean square error of approximation (RMSEA) = 0.116], whereas separate proposed 3-factor solutions with varying item scoring fit marginally well (RMSEA = 0.080, 0.089). The CFA suggests the existence of a third dimension, social, beyond the established original two-factor solution. Results suggest in a direct comparison of proposed social dimensions, both Garin's four item solution and Munyombwe's six-item solution provide similar results. CONCLUSIONS: Results suggest support for an additional third factor among patients undergoing isolated valve replacement surgery. We suggest given the inclusion of items important to our population, relatively strong fit indices, and correlation with the SF-12, the social dimension proposed by Munyombwe best fits our population.

Pathological Remodeling of Mitral Valve Leaflets from Unphysiologic Leaflet Mechanics after Undersized Mitral Annuloplasty to Repair Ischemic Mitral Regurgitation.

Background Undersized ring annuloplasty is a commonly used surgical repair for ischemic mitral regurgitation, in which annular downsizing corrects regurgitation, but alters valve geometry and elevates tissue stresses. In this study, we investigated if unphysiological leaflet kinematics after annuloplasty might cause pathogenic biological remodeling of the mitral valve leaflets, and if preserving physiologic leaflet kinematics with a better technique can moderate such adverse remodeling. Methods and Results Twenty-nine swine were induced with ischemic mitral regurgitation, and survivors were assigned to groups: 7 underwent annuloplasty, 12 underwent annuloplasty with papillary-muscle approximation, 6 underwent papillary-muscle approximation, and 3 were sham controls. Pre-and post-surgery leaflet kinematics were measured, and valve tissue was explanted after 3 months to assess biological changes. Anterior leaflet excursion was unchanged across groups, but persistent tethering was observed with annuloplasty. Posterior leaflet was vertically immobile after annuloplasty, better mobile with the combined approach, and substantially ( P=0.0028) mobile after papillary-muscle approximation. Procollagen-1 was higher in leaflets from annuloplasty compared with the other groups. Heat shock protein-47 and lysyl oxidase were higher in groups receiving annuloplasty compared with sham. α- SMA was elevated in leaflets from animals receiving an annuloplasty, indicating activation of quiescent valve interstitial cells, paralleled by elevated transforming growth factor-ß expression. Conclusions This is the first study to demonstrate that surgical valve repairs that impose unphysiological leaflet mechanics have a deleterious, pathological impact on valve biology. Surgeons may need to consider restoring physiologic leaflet stresses as well as valve competence, while also exploring pharmacological methods to inhibit the abnormal signaling cascades.

Video and accelerometer-based motion analysis for automated surgical skills assessment.

PURPOSE: Basic surgical skills of suturing and knot tying are an essential part of medical training. Having an automated system for surgical skills assessment could help save experts time and improve training efficiency. There have been some recent attempts at automated surgical skills assessment using either video analysis or acceleration data. In this paper, we present a novel approach for automated assessment of OSATS-like surgical skills and provide an analysis of different features on multi-modal data (video and accelerometer data). METHODS: We conduct a large study for basic surgical skill assessment on a dataset that contained video and accelerometer data for suturing and knot-tying tasks. We introduce "entropy-based" features-approximate entropy and cross-approximate entropy, which quantify the amount of predictability and regularity of fluctuations in time series data. The proposed features are compared to existing methods of Sequential Motion Texture, Discrete Cosine Transform and Discrete Fourier Transform, for surgical skills assessment. RESULTS: We report average performance of different features across all applicable OSATS-like criteria for suturing and knot-tying tasks. Our analysis shows that the proposed entropy-based features outperform previous state-of-the-art methods using video data, achieving average classification accuracies of 95.1 and 92.2% for suturing and knot tying, respectively. For accelerometer data, our method performs better for suturing achieving 86.8% average accuracy. We also show that fusion of video and acceleration features can improve overall performance for skill assessment. CONCLUSION: Automated surgical skills assessment can be achieved with high accuracy using the proposed entropy features. Such a system can significantly improve the efficiency of surgical training in medical schools and teaching hospitals.

Operative strategies to reduce cerebral embolic events during on- and off-pump coronary artery bypass surgery: A stratified, prospective randomized trial.

OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy. Transcranial Doppler ultrasonography (TCD) was performed to identify high-intensity transient signals (HITS) in the middle cerebral arteries during periods of aortic manipulation. Neurocognitive testing was performed at baseline and 30-days postoperatively. The primary endpoint was total number of HITS detected by TCD. Groups were compared using the Mann-Whitney U test. RESULTS: In the off-pump group, the median number of total HITS were higher in the CFD subgroup (30.0; interquartile range [IQR], 22-43) compared with the partial clamp subgroup (7.0; IQR, 0-16; P < .0001). In the CFD subgroup, the median number of total HITS was significantly lower for patients with 1 CFD compared with patients with >1 CFD (12.5 [IQR, 4-19] vs 36.0 [IQR, 25-47]; P = .001). In the on-pump group, the median number of total HITS was 10.0 (IQR, 3-17) in the single-clamp group, compared with 16.0 (IQR, 4-49) in the double-clamp group (P = .10). There were no differences in neurocognitive outcomes across the groups. CONCLUSIONS: For patients with low-grade aortic disease, the use of CFDs was associated with an increased rate of cerebral embolic events compared with partial clamping during off-pump CABG. A single-clamp strategy during on-pump CABG did not significantly reduce embolic events compared with a double-clamp strategy.

A Swine Model of Percutaneous Intracoronary Ethanol Induced Acute Myocardial Infarction and Ischemic Mitral Regurgitation.

Ischemic mitral regurgitation (IMR) is a frequent complication after a myocardial infarction (MI), which doubles mortality. Transcatheter mitral repairs are emerging as alternative treatment options to open heart surgery for IMR, but animal models to test them are lacking. We report a percutaneous swine model of IMR. Seventeen swine were randomized to (group 1, n = 12) MI causing IMR, and (group 2, n = 5) controls. In group 1, MI was induced via percutaneous ethanol injection into the obtuse marginal branches of the left circumflex artery, resulting in ST elevating myocardial infarction. Nine animals were survived to 8-10 weeks with weekly echocardiograms and three swine were survived to 16-20 weeks with MRI at termination. In group 1 animals, average IMR fraction at termination was 26.6 ± 2.3% in the echo group, and 24.51 ± 0.41% in the MRI group. None of the animals in group 2 had IMR. Left ventricular dysfunction and significant dilatation were evident in group 1 animals, compared to the controls. In conclusion, a reproducible model of IMR is reported for use in pre-clinical testing of new mitral technologies.

End-stage renal disease and severe aortic stenosis: Does valve replacement improve one-year outcomes?

BACKGROUND: Treatment for patients with end-stage renal disease (ESRD) and severe aortic stenosis (AS) includes balloon aortic valvuloplasty (BAV), surgical (SAVR), or transcatheter (TAVR) aortic valve replacement. We compared outcomes among these strategies. METHODS: A retrospective review of patients with ESRD undergoing treatment for severe AS between 07/2007 and 06/2015 was performed at our center. Patients were classified based on treatment: BAV-only, TAVR, or SAVR. Baseline characteristics and 30-day outcomes were compared among groups. A 1-year survival analysis was performed. RESULTS: Of 85 patients, 25 (29.4%) underwent BAV, 30 (35.3%) TAVR, and 30 (35.3%) SAVR. Patients in the SAVR group, compared to the BAV or TAVR patients, were younger (63 vs. 74 vs. 71 years, P = 0.02) and had less prior stroke (3.3% vs. 12.0% vs. 30.0%, P = 0.008). While all BAV patients had NYHA class III/IV, 93.3% and 76.7% of patients had NYHA class III/IV in the TAVR and SAVR group, respectively (P = 0.001). BAV patients were less likely to have atrial fibrillation than TAVR or SAVR patients (16.0% vs. 43.3% vs. 50.0%, P = 0.03). All patients were high risk, but there was a statistical trend to lower STS scores in the SAVR group (8.6% vs. 13.5% vs. 13.5%, P = 0.08). There was no significant difference in 30-day mortality (16.7% vs. 10.0% vs. 10.0%, P = 0.74), but BAV treated patients had an increased 1-year mortality compared to those treated with TAVR or SAVR (87.0% vs. 32.0%, vs. 36.7%, P=<0.001). Independent predictors of 1-year mortality were a higher STS score (HR 1.026, 95%CI 1.002-1.051) and BAV-only strategy (BAV vs. TAVR: HR 3.961, 95%CI 1.595-9.840), but dialysis duration and type, and SAVR versus TAVR were not. CONCLUSIONS: Patients with ESRD and severe AS have a similar and higher survival with TAVR or SAVR when compared to BAV at 1-year. These results may influence patient care decisions favoring valve replacement in AS patients with ESRD. © 2016 Wiley Periodicals, Inc.

Transcatheter Mitral Valve Repair Therapies: Evolution, Status and Challenges.

Mitral regurgitation is a common cardiac valve lesion, developing from primary lesions of the mitral valve or secondary to cardiomyopathies. Moderate or higher severity of mitral regurgitation imposes significant volume overload on the left ventricle, causing permanent structural and functional deterioration of the myocardium and heart failure. Timely correction of regurgitation is essential to preserve cardiac function, but surgical mitral valve repair is often delayed due to the risks of open heart surgery. Since correction of mitral regurgitation can provide symptomatic relief and halt progressive cardiac dysfunction, transcatheter mitral valve repair technologies are emerging as alternative therapies. In this approach, the mitral valve is repaired either with sutures or implants that are delivered to the native valve on catheters introduced into the cardiovascular system under image guidance, through small vascular or ventricular ports. Several transcatheter mitral valve technologies are in development, but limited clinical success has been achieved. In this review, we present a historical perspective of mitral valve repair, review the transcatheter technologies emerging from surgical concepts, the challenges they face in achieving successful clinical application, and the increasing rigor of safety and durability standards for new transcatheter valve technologies.

The Racial Paradox in Multiarterial Conduit Utilization for Coronary Artery Bypass Grafting.

BACKGROUND: It has been established that outcomes for black patients undergoing coronary artery bypass graft surgery (CABG) are inferior to those of their white counterparts. The purpose of this study was to determine (1) whether rates of multiarterial grafting are different among black patients and white patients, and (2) whether racial differences exist in postoperative outcomes after accounting for grafting strategy. METHODS: A retrospective review of black patients (n = 2,810) and white patients (n = 13,569) who underwent isolated, primary CABG from January 2002 to June 2014 at a US academic institution was performed. A modified predicted risk of mortality (M-PROM) score was calculated for each patient using all The Society of Thoracic Surgeons variables for CABG excluding race. Multivariable linear, logistic, and Cox regression analyses were used to assess between-group differences, adjusted for M-PROM. RESULTS: Overall, 16,379 patients underwent CABG, and 2,441 (14.9%) received more than one arterial graft. When adjusted for M-PROM, the odds of blacks undergoing multiarterial CABG were 10% greater than for whites (p = 0.05). Blacks had worse inhospital outcomes, including higher odds of stroke (odds ratio 2.41, 95% confidence interval [CI]: 1.80 to 3.25) and prolonged intubation (odds ratio 2.01, 95% CI: 1.77 to 2.28). The increase in postoperative complications did not translate to a difference in inhospital mortality (p = 0.10) between racial cohorts. Moreover, among patients who underwent multiarterial grafting strategies, blacks had a hazard of mortality that was 34% higher (95% CI: 22% to 51%)) than that of their white counterparts. Among black patients, those who underwent multiarterial grafting strategies showed better long-term survival than those undergoing single grafting strategies (hazard ratio 0.86, 95% CI: 0.78 to 0.96). CONCLUSIONS: Despite similar rates of arterial grafting for black patients and white patients in this large single-center cohort, black patients continued to have significantly worse late survival when compared with white patients. Continued evaluation as to the causes of this disparity is warranted.

Should We Perform Carotid Doppler Screening Before Surgical or Transcatheter Aortic Valve Replacement?

BACKGROUND: Screening for internal carotid artery stenosis (ICAS) with Doppler ultrasound is commonly used before cardiovascular surgery. Nevertheless, the relationship between ICAS and procedure-related stroke in isolated aortic valve replacement is unclear. METHODS: We retrospectively reviewed patients with artery stenosis who underwent ICAS screening before surgical (SAVR) or transcatheter aortic valve replacement (TAVR) between January 2007 and August 2014. Logistic regression models were used to determine the relation between post-procedure stroke and total (sum of left and right ICAS) and maximal unilateral ICAS. Age, sex, history of atrial fibrillation, cerebrovascular disease and diabetes, left ventricular ejection fraction, and procedure type were considered as covariates. Two-subgroup analyses were performed in patients who underwent TAVR and SAVR, adjusting for procedure specific details. RESULTS: A total of 996 patients underwent ICAS screening before TAVR (n = 467) or SAVR (n = 529). The prevalence of at least ≥70% ICAS was 5.2% (n = 52) and incidence of 30-day stroke was 3.4% (n = 34). Eight patients who underwent carotid intervention before valve replacement and 6 patients with poor Doppler images were excluded from the final analysis. We found no statistically significant association between stroke and either the total or maximal unilateral ICAS for all patients (p = 0.13 and p = 0.39, respectively) or those undergoing TAVR (p = 0.27 and p = 0.63, respectively) or SAVR (p = 0.21 and p = 0.36, respectively). CONCLUSIONS: We found no statistically significant association between ICAS severity procedure-related stroke after aortic valve replacement. This suggests that universal carotid Doppler screening before isolated TAVR or SAVR is unnecessary.